Toll-like receptors are expressed by a variety of cancers, including T-cell ALL (T-ALL) and melanoma. Acute lymphoblastic leukemia (ALL) accounts for approximately 30% of cancers in children, making it the most common cancer in this age group (0-19 years) (1-3). T-ALL accounts for approximately 30% of all ALL cases. The use of conventional cancer therapies has resulted in a complete remission rate of approximately 75% in childhood T-ALL. In adults however, the 5-year survival rate is only 45-55%. Furthermore, T-ALL patients are also at increased risk of early recurrence and CNS relapse. The prognosis for relapsing patients is poor, with approximately 15% to 25% achieving stable remission after second-line treatment because of drug resistance and limited effective therapeutic options (2). Of note, unlike B-cell ALL, factors such as older age and a high white blood cell count are not reliable predictors in patients with T-ALL, rendering this patient population high-risk.
In addition to T-ALL, malignant melanoma is a life-threatening and aggressive type of skin cancer. Melanoma is the fifth most common cancer and is responsible for more than 75 percent of skin cancer-related deaths (39-40). The incidence of melanoma continues to rise world-wide but the development of new therapeutic agents has not kept up with the increased cancer occurrences. The median survival of patients with advanced disease is approximately 6 months and the survival rate at 5 years is 6% (39-40). Currently, there is no effective cure for patients with advanced melanoma. This is due in large part to their high resistance to chemotherapeutic drugs. Treatment failure is attributed to melanoma's resistance to all existing forms of cancer therapies.
Therefore, a need exists for the development of effective therapies and an ability to predict disease recurrence and therapy resistance in cancers such as T-ALL and melanoma.